Nepetalactone is an effective active ingredient for insect repellents. Current ingredients used for insect repellence such as N, N-Diethyl-meta-toluamide (DEET) pose health concerns, while other natural alternatives only offer short-term protection. Nepetalactone is derived primarily from the plant Nepeta cataria, but is produced at low levels. Yields are subject to environmental factors, such as climate and pests, creating an unreliable supply for broad use beyond acting as a cat attractant. Chemical synthesis is feasible, but not economical.
An approach to creating a more dependable supply of nepetalactone is to genetically engineer a microbial host for production of this chemical from glucose or to express one or more of the necessary enzymes, either in cell culture or in a cell-free protein expression system, which can be employed in a chemoenzymatic process for producing nepetalactone. A number of biochemical steps and the corresponding genetic elements have already been characterized to indirectly demonstrate the production of the nepetalactone precursor nepetalactol as an intermediate to a different natural product, strictosidine, in a microbial host. However, prior to the present work, the full pathway has not been recapitulated in any microorganism, and no efficient chemoenzymatic process for nepetalactone production from a precursor has been described.